Biomedical subjects

H Karlsson

Publications and source records attributed to H Karlsson.

At least 19 recordsLinked to original sources

PubMed1998

Heparin ameliorates pulmonary hypertension induced by platelet-activating factor in pigs.

The purpose of this study was to investigate the effects of heparin on the haemodynamic changes which were induced by platelet-activating factor in the pulmonary and systemic circulation in pigs. Mean arterial pressure and mean pulmonary arterial pressure were measured continuously in five anaesthetised juvenile pigs. Bolus doses of platelet-activating factor (0.2-2 microg) were given intravenously to establish a dose response curve. Heparin (300 units/kg) was given intravenously. Thirty minutes later, the same doses of platelet-activating factor were repeated to establish a second dose response curve. Platelet-activating factor caused a dose dependent pulmonary artery hypertension, associated with an initial systemic hypotension followed by systemic hypertension. Heparin effectively reduced the low dose (0.2 microg) platelet-activating factor-induced pulmonary arterial hypertension (p<0.01) but not the higher doses. It had no effect on the platelet-activating factor-induced systemic hypotension or hypertension. The pulmonary and systemic circulation responded differently to platelet-activating factor after giving heparin. While heparin ameliorated the platelet-activating factor-induced pulmonary hypertension, it did not affect the changes in the systemic circulation.

Animals↗

PubMed1998

Different O-glycosylation of respiratory mucin glycopeptides from a patient with cystic fibrosis.

The O-linked oligosaccharides from three fractions of highly glycosylated mucin glycopeptides obtained from sputum of a patient with cystic fibrosis were characterized and compared regarding size, composition, sequence and when possible linkage positions. Neutral and sialic acid-containing glycans were permethylated and analyzed by high-temperature GC-MS and MALDI-MS, showing more than 60 different oligosaccharides with a size of up to 15 monosaccharide units. Some of the observed oligosaccharides are novel for respiratory secretions, one being a trifucosylated heptasaccharide with the proposed structure: Fuc-Gal-4(Fuc-3)GlcNAc-(Fuc-)Gal-3GalNAcol. The glycosylation of two of the glycopeptide fractions was similar with regard to the neutral and sialylated oligosaccharides despite their different origins from the sol or gel phase. Analysis of the sulfated oligosaccharides by FAB-MS/MS indicated that the gel fraction contained C-6 linked sulfate groups while the two sol fractions also contained C-3 linked sulfate. The results suggest the presence of different glycosylated mucin domains, probably originating from different mucin glycoforms and/or apoproteins in the airway of cystic fibrosis patients.

Adolescent↗

PubMed1998

Rapid and sensitive GC/MS characterization of glycolipid released Galalpha1,3Gal-terminated oligosaccharides from small organ specimens of a single pig.

Pig to human xenotransplantation is considered a possible solution to the prevailing chronic lack of human donor organs for allotransplantation. The Galalpha1,3Gal determinant is the major porcine xenogeneic epitope causing hyperacute rejection following human antibody binding and complement activation. In order to characterize the tissue distribution of Galalpha1,3Gal-containing and blood group-type glycosphingolipids in pig, acid and nonacid glycosphingolipids were isolated from the kidney, small intestine, spleen, salivary gland, liver, and heart of a single pig obtained from a semi-inbred strain homozygous at the SLA locus. Glycolipids were analyzed by thin-layer immunostaining using monoclonal antibodies, and following ceramide glycanase cleavage as permethylated oligosaccharides by gas chromatography, gas chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. The kidney contained large amounts of Galalpha1,3Gal-containing penta- and hexasaccharides having carbohydrate sequences consistent with the Galalpha1,3nLc4and Galalpha1,3Lexstructures, respectively. The former structure was tentatively identified in all organs by GC/MS. The presence of extended Galalpha1,3Gal-terminated structures in the kidney and heart was suggested by antibody binding, and GC/MS indicated the presence of a Galalpha1,3nLc6structure in the heart. The kidney, spleen, and heart contained blood group H pentaglycosylceramides based on type 1 (H-5-1) and type 2 (H-5-2) chains, and H hexaglycosylceramides based on the type 4 chain (H-6-4). In the intestine H-5-1 and H-6-4 were expressed, in the salivary gland H-5-1 and H-5-2, whereas only the H-5-1 structure was identified in the liver. Blood group A structures were identified in the salivary gland and the heart by antibody binding and GC/MS, indicating an organ-specific expression of blood group AH antigens in the pig.

Animals↗

PubMed1997

Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone.

Growth hormone (GH) binding to its receptor modulates gene transcription by influencing the amount or activity of transcription factors. In the rat, GH exerts sexually dimorphic effects on liver gene transcription through its pattern of secretion which is intermittent in males and continuous in females. The expression of the CYP2C12 gene coding for the female-specific cytochrome P450 2C12 protein is dependent on the continuous exposure to GH. To identify the transcription factor(s) that mediate(s) this sex-dependent GH effect, we studied the interactions of the CYP2C12 promoter with liver nuclear proteins obtained from male and female rats and from hypophysectomized animals treated or not by continuous GH infusion. GH treatment induced the binding of a protein that we identified as hepatocyte nuclear factor (HNF) 6, the prototype of a novel class of homeodomain transcription factors. HNF-6 competed with HNF-3 for binding to the same site in the CYP2C12 promoter. This HNF-6/HNF-3 binding site conveyed both HNF-6- and HNF-3-stimulated transcription of a reporter gene construct in transient cotransfection experiments. Electrophoretic mobility shift assays showed more HNF-6 DNA-binding activity in female than in male liver nuclear extracts. Liver HNF-6 mRNA was barely detectable in the hypophysectomized rats and was restored to normal levels by GH treatment. This work provides an example of a homeodomain-containing transcription factor that is GH-regulated and also reports on the hormonal regulation of HNF-6.

Animals↗

PubMed1997

FK506 suppresses the mitogen-induced increase in lymphocyte adhesiveness to endothelial cells, but does not affect endothelial cell activation in response to inflammatory stimuli.

BACKGROUND: In vivo studies indicate that FK506 may affect endothelial cell activation. FK506 has also been reported to affect leukocyte adhesiveness and transendothelial migration. The purpose of the present study was to investigate the direct effects of FK506 on endothelial activation and on the increase in lymphocyte adhesiveness associated with mitogen stimulation. METHODS: Using flow cytometry and enzyme-linked immunosorbent assays, we studied the effects of FK506 on expression of E-selectin and intercellular adhesion molecule 1 and on the release of interleukin (IL) 6 and IL-8 from endothelial cells in response to inflammatory mediators. Expression of lymphocyte adhesion molecules and adhesion between lymphocytes and endothelial cells were also quantitated using flow cytometry. RESULTS: Endothelial activation in response to lipopolysaccharide, IL-1beta, or tumor necrosis factor-alpha was found to be unaffected by FK506. The increase in lymphocyte adhesiveness to endothelium seen after mitogen stimulation, on the other hand, was significantly depressed by FK506. The associated changes in the expression of CD11c, CD29, and CD31 were also significantly altered by FK506. CONCLUSION: In addition to its inhibitory effects on T-cell activation, FK506 may also interfere with processes leading to increased lymphocyte adhesiveness. This is thus a possible additional mechanism for its beneficial effects in connection with organ rejection and autoimmune diseases.

Cell Adhesion↗

PubMed1997

The glycosylation of rat intestinal Muc2 mucin varies between rat strains and the small and large intestine. A study of O-linked oligosaccharides by a mass spectrometric approach.

The large glycosylated domains obtained from the rat intestinal mucin Muc2 were isolated from the large and small intestine of the inbred rat strains GOT-W and GOT-BW. The expression of the rat Muc2 in the large intestine was confirmed immunochemically and by Northern blotting. Released oligosaccharides were structurally characterized by gas chromatography-mass spectrometry (neutral and sialylated species) or by tandem mass spectrometry (sulfated species), and a total of 63 structures was assigned. The large intestinal oligosaccharides were found to be identical between the strains, while the small intestinal glycosylation differed. Until now, detailed structural analysis of oligosaccharides isolated from a single mucin core or mucin domain with different origin have not been performed, and the information of different mucin glycoforms has been limited to immunochemistry. Blood group A-determinants (GalNAcalpha1-3(Fucalpha1-2)Galbeta1-, and structures related to the blood group Sda/Cad-related epitope NeuAc/NeuGcalpha1-3(GalNAcbeta1-4)Galbeta1-, were found in GOT-BW small intestine, and also in both large intestines. Blood group H-determinants and NeuAc/NeuGcalpha1-3Galbeta1- were found in all samples. Core 1 (Galbeta1-3GalNAcalpha1-), core 2 (Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-), core 3 (GlcNAcbeta1-3GalNAcalpha1-), and core 4 (GlcNAcbeta1-3(GlcNAcbeta1-6)GalNAcalpha1- were also found in all the samples. The large intestine were enriched in sulfated oligosaccharides and the small intestine contained higher amounts of sialylated species. Sulfation were found exclusively on C-6 of GlcNAc.

ABO Blood-Group System↗

PubMed1997

Glycosylation differences between pig gastric mucin populations: a comparative study of the neutral oligosaccharides using mass spectrometry.

Five mucin populations were isolated from the cardiac region,corpus and antrum of pig gastric mucosa. The released neutral oligosaccharides were permethylated and analysed using high-temperature gas chromatography-mass spectrometry (GC-MS) as well as matrix-assisted laser-desorption mass spectrometry (MALDI-MS). Thirty different oligosaccharides with up to six monosaccharide residues were characterized using both techniques, but the presence of an additional 49 structures was suggested on the basis of their molecular mass by MALDI-MS. Oligosaccharides based on core-1 (Galbeta1-3GalNAcalpha1-) and core-2 [Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] structures were widely distributed, whereas core-3 structures (GlcNAcbeta1-3GalNAcalpha1-) were present only in mucins from the cardiac region and corpus, and core-4 structures [GlcNAcbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-] were present exclusively in mucins from the cardiac region. Furthermore the oligosaccharides from one of the mucins from the corpus were significantly longer than those from the other populations. The results illustrate vast structural diversity, but the relative abundances show only a few dominating structures, suggesting that many oligosaccharides may be quite rare in pig gastric mucins. Well-defined mucin populations with distinctly different glycosylation can thus be identified in pig stomach, suggesting that glycosylation of the large secreted mucins from this tissue is not a random event.

Animals↗

PubMed1997

Energy levels in resting and mitogen-stimulated human lymphocytes during treatment with FK506 or cyclosporin A in vitro.

By employing microcalorimetry to assess overall metabolic activity in combination with other assays for specific metabolic events, we have investigated the influence of cyclosporin A and FK506 on the metabolic status of resting and mitogen-stimulated human peripheral lymphocytes. Both cyclosporin A and FK506 significantly reduced heat output from resting lymphocytes. This reduction could not be correlated with effects on DNA synthesis, lactate production, ATP levels or mitochondrial uptake of Rhodamine 123. These two drugs also potently reduced the increase in heat output seen during mitogen stimulation of lymphocytes. Both cyclosporin A and FK506 also prevented the increase in DNA synthesis, lactate production and ATP levels seen in response to mitogen stimulation. The increase in mitochondrial uptake of Rhodamine 123 during blastoid transformation was significantly reduced only by cyclosporin A. We ascribe the major part of the effects of these compounds to inhibition of the glycolytic pathway in both resting and mitogen-stimulated lymphocytes. These results indicate that the immunosuppressants cyclosporin A and FK506 exert other effects on lymphocytes than their well-established inhibitory action on calcineurin.

Adenosine Triphosphate↗

PubMed1997

Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.

BACKGROUND: We hypothesized that myocardial content of alpha-ketoglutarate (alpha-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of alpha-KG could reduce metabolic abnormalities and lead to improved myocardial protection. METHODS: Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of alpha-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured. RESULTS: alpha-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 +/- 2.4 microg/L versus 49 +/- 4.9 microg/L (creatine kinase isoenzyme MB) and 1.1 +/- 0.05 microg/L versus 2.0 +/- 0.34 microg/L (troponin T). Myocardial oxygen extraction was higher during alpha-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the alpha-KG-treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion. CONCLUSION: Provision of alpha-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.

Aged↗

PubMed1997

Frequent attender profiles: different clinical subgroups among frequent attender patients in primary care.

Psychiatric and physical morbidity among frequently attending patients in primary care is high. However, very few efforts have been made to sort out the complex patterns of problems these patients have. We developed a clinical grouping of these patients. Our sample consisted of 67 frequent attenders. The measures included physical and psychiatric illnesses, presenting symptoms, sociodemographic data, psychosocial situation, level of distress, global functioning, experienced life satisfaction, illness attribution, and current psychiatric treatment. We identified five groups with different profiles: (1) patients with entirely physical illnesses; (2) patients with clear psychiatric illnesses; (3) crisis patients; (4) chronically somatizing patients; and (5) patients with multiple problems. The grouping was based on multidimensional operational criteria. The majority in all groups attended for solely physical illnesses or symptoms suggesting different forms of somatization. Only a few patients were undergoing any psychiatric treatment. Differences between groups were found regarding sociodemographic factors, physical illnesses, global functioning, and satisfaction.

Adolescent↗

PubMed1997

Psychiatric morbidity in primary public health care: a multicentre investigation. Part II. Hidden morbidity and choice of treatment.

A total of 1,281 patients were examined during consultation with their GP in a Nordic multicentre study focusing on the prevalence of psychiatric illness, hidden psychiatric morbidity, treatment and pathways to specialized care. The methodology and prevalence were reported in an accompanying paper. The present paper presents results concerning the variables hidden psychiatric morbidity, treatment and pathways to specialized care. The GPs detected 44% of the psychiatric cases compared with the result of a diagnostic interview (PSE). The distinction between psychosis and non-psychosis did not influence the GPs' ability to detect a mental illness. According to the GPs' assessment the majority of patients suffering from a mental disorder consulted their GP about physical complaints. The GPs treated the patients themselves, and only a limited number of cases were referred to psychiatrists or psychologists.

Adolescent↗

PubMed1996

A calorimetric method for continuous recording of lymphocyte proliferation.

We have developed a calorimetric technique as an alternative non-radioactive method for measuring mitogen-induced lymphocyte proliferation. Power-time curves can be recorded from as few as 2X10(5) cells suspended in 4 ml medium. This density is, however, too low for the detection of proliferation during a 72 h incubation. Cell numbers exceeding 4X10(6) suspended in 4 ml medium cause pronounced crowding and are therefore too high for use during proliferation studies. We found the optimal initial cell concentration to be 2X10(6) cells suspended in 4 ml of medium. In a four-channel bioactivity monitor, up to four separate incubations can be run in parallel. Furthermore, this method offers the advantage of one-line monitoring of cell proliferation throughout the incubation.

Calorimetry↗

PubMed1996

Sulphated mucin oligosaccharides from porcine small intestine analysed by four-sector tandem mass spectrometry.

The fraction of sulphated oligosaccharide alditols isolated from mucin glycopeptides of porcine small intestine 'insoluble' mucin complex was analysed by negative-ion fast atom bombardment (FAB) tandem mass spectrometry. Collision-induced dissociation (CID) tandem mass spectra of native and peracetylated species were compared with standards of sulphated monosaccharides. The tandem mass spectra revealed structural information of the carbohydrate sequence and sulphate position. Negative-ion FAB ionization of the peracetylated sulphated oligo-saccharide alditols was at least three times more sensitive than that of the native sulphated oligosaccharide alditols, as revealed by comparing the signal-to-noise ratios, and allowed the detection of eleven compared with six pseudo-molecular ions. Fourteen structures were determined from the CID tandem mass spectra obtained. The main sulphation site was C-6 of an N-acetylglucosamine 6-linked to the N-acetylgalactosaminitol. C-3 of the N-acetylgalactosaminitol could be unsubstituted or extended with a series of up to three monosaccharide residues including blood group H determinants and blood group A determinants. Also, the sulphated N-acetylglucosamine could be further extended. The most abundant structure was a monosulphated trisaccharide with the sequence Gal-->3(SO3-->6GlcNAc-->6)GalNAcol. The sulphation at C-6 of N-acetylglucosamine seems to be a common feature for O-linked oligosaccharides, and has been described both for skeletal keratan sulphates and respiratory mucin oligosaccharides. Low-abundance ions were also detected from oligosaccharides with sulphation at C-3 of an amino sugar residue. This seems to be a novel sulphation site for mucin oligosaccharides.

Acetylation↗

PubMed1996

Molecular characterization of the large heavily glycosylated domain glycopeptide from the rat small intestinal Muc2 mucin.

The largest high-glycosylated domain, glycopeptide A, of the "insoluble' mucin complex of the rat small intestine has earlier been purified and characterized (Carlstedt et al., 1993, J Biol Chem 268: 18771-81). A rabbit antiserum raised against deglycosylated glycopeptide A was used to clone part of a mucin showing homology to the human MUC2 mucin (Hansson et al., 1994, Biochem Biophys Res Commun 198. 181-90). This serum specifically stained goblet cells (paranuclear) in the mouse small intestine. The size of the coding sequence of glycopeptide A was estimated by using reversed transcriptase PCR of mRNA from an inbred rat strain (GOT-W) using primers in the unique central and C-terminal parts of the proposed rat Muc2 sequences. The PCR and Southern blot of the PCR products showed a fragment of about 5.5 kb corresponding to about 1700 amino acids when the known Cys-rich sequences used for the primers were subtracted. This is slightly larger than the size estimated earlier by biochemical studies. The mRNA encoding the rat Muc2 was slightly smaller than the mRNA encoding the human MUC2 in a colorectal cell line. Although the size of glycopeptide A estimated from biochemical results and by PCR is not identical, the results obtained here further support that the "insoluble' mucin of the rat small intestine is encoded by the Muc2 gene. Most of the oligosaccharides in glycopeptide A were either neutral (40%) or sialylated (40%). The remaining ones were sulfated with the sulfate group attached to C-6 of N-acetylglucosamine linked to C-6 of the N-acetylgalactosaminitol as revealed by tandem mass spectrometry of the perdeuteroacetylated oligosaccharides. Eighteen oligosaccharides were found of which fourteen were characterized and found to be mostly novel. Our findings thus expand the current knowledge of the core peptide of the rat intestinal goblet cell mucin and provide a relatively complete picture of the glycosylation of a defined mucin domain.

Animals↗

PubMed1996

Regional skin temperature, heat flow and conductance in preterm neonates nursed in low and in neutral environmental temperature.

The changes of regional dry heat loss and skin temperature in 15 healthy preterm babies, 8 with a gestational age (GA) of 33-36 weeks and 7 with a GA of 28-31 weeks, were studied under controlled conditions at environmental temperatures ranging from 29.5 to 34.0 degrees C. In both groups of babies the skin temperature for all body regions followed the changes in operative temperatures. Regional dry heat losses also closely followed the external temperature gradient. In the 33-36 weeks GA neonates the regional changes in thermal conductance (index of cutaneous blood flow) indicated that only the foot responded to low environmental temperature with vasoconstriction while vasodilatation was indicated for the trunk. In the 28-31 weeks GA neonates similar but not significant changes of thermal conductance were calculated. The limited ability to reduce heat loss by reducing the skin conductance over a major part of the body surface area contributes to the vulnerability to low environmental temperature in preterm neonates.

Body Surface Area↗

PubMed1996

Skin to skin care:heat balance.

Skin to skin care has been practised in primitive and high technology cultures for body temperature preservation in neonates. Regional skin temperature and heat flow was measured in moderately hypothermic term neonates to quantitate the heat transfer occurring during one hour of skin to skin care. Nine healthy newborns with a mean rectal temperature of 36.3 degrees C were placed skin to skin on their mothers' chests. The mean (SD) rectal temperature increased by 0.7 (0.4) degrees C to 37.0 degrees C. The heat loss was high (70 Wm-2) from the unprotected skin of the head to the surrounding air. Minute heat losses occurred from covered areas; and heat was initially gained from areas in contact with the mother's skin. The total dry heat loss during skin to skin care corresponded to heat loss during incubator care at 32-32.5 degrees C. The reduced heat loss, and to a minor extent, the initial heat flux from the mothers allowed heat to be conserved, leading to rewarming.

Body Temperature Regulation↗

PubMed1996

Alexithymia and psychological distress among frequent attendance patients in health care.

BACKGROUND: The aim of the present study was to find out whether alexithymia is common in frequently attending primary health care patients and whether alexithymia and psychological distress are associated in these patients. METHODS: Alexithymia was measured by the TAS-26 and psychological distress by the SCL-25 in a random sample of 394 working-age primary health care patients. Frequent attendance was defined as a minimum of 11 visits during 1 year to different kinds of outpatient health care services, excluding specialized psychiatric care. RESULTS: Frequently attending patients with psychological distress were found to be alexithymic more commonly than other patients, but this was not the case with other frequently attending patients. In other words, frequent attendance and alexithymia had an association mediated by psychological distress. CONCLUSIONS: There is a subgroup of frequently attending patients, who are alexithymic and have psychological distress, too. They usually visit health-care services because of a somatic complaint. We hypothesize that their expression of psychological distress was masked and somatized just because of alexithymia.

Adolescent↗

PubMed1995

Separation and detection of 4-hexadecylaniline maltooligosaccharide derivatives with packed capillary liquid chromatography-frit fast atom bombardment-mass spectrometry.

A LC-MS method is under development for the separation and detection of mixtures of native glycolipids and of oligosaccharide derivatives. The LC system is based on slurry-packed capillary columns. Frit fast atom bombardment (frit-FAB) is used as the LC-MS interface and ionisation technique and the column is connected to the frit via a 50 microns I.D. fused-silica capillary liner. Post column addition of matrix is achieved using a 50 microns I.D. fused-silica capillary liner with 2.5% (v/v) matrix solution. The two liners are joined through a septum and end side by side against the frit. The detection limit was found to be less than 1 pmole in the negative ion mode. A mixture of tetra to deca maltooligosaccharides reductively aminated with 4-hexadecylaniline (M4-10-HDA) was separated on a straight phase silica column using gradient elution.

Aniline Compounds↗